Large case-control study indicates no association of KIR genotype and risk of developing acute myeloid leukemia

Immunogenetic association studies may give rise to new hypotheses on the immune surveillance of cancer. We hypothesized that certain combinations of Killer-cell Immunoglobulin-like Receptor (KIR) and HLA genotypes may enhance Natural Killer (NK)-cell immunity against nascent acute myeloid leukemia (AML) and thereby lead to a skewed genotype distribution among patients. For this purpose, we analyzed KIR and HLA genotypes of 1767 German patients with AML and compared the results to data of 51 890 German volunteers who had registered with DKMS. Patient samples were retrieved from the Collaborative Biobank (CoBi) and the Biorepository of the Study Alliance Leukemia (SAL). All samples were genotyped with high-resolution amplicon-based next-generation sequencing. Owing to the large number of controls this study was very sensitive to detect an impact of KIR genotype. Knowledge on KIRs and their cognate HLA ligands allowed for testing of several hypotheses of NK-cell mediated endogenous leukemia surveillance. We did not find significant differences between the two cohorts regarding presence or absence of single KIR genes. When grouped by telomeric or centromeric gene content, the major haplotypes A/A, A/B, and B/B were equally distributed among patients and controls. Using information on KIRs and their HLA ligands, we further tested receptor-ligand models and summation models without revealing markedly significant differences between patients and controls, albeit we observed a trend pointing at a minor protective effect of a low number of inhibitory KIR/KIR-ligand pairs. The results suggest that the KIR/KIR-ligand genotype has no effect on the susceptibility for the development of de novo AML.